Pediatric Antimicrobial Stewardship: Smart Choices for Tiny Warriors

---

Antimicrobial resistance (AMR) is a growing health crisis, contributing significantly to morbidity and mortality in adults and children.^1,2 Specifically, a recent study estimated that more than 1 million deaths worldwide can be attributed to bacterial AMR, and the CDC released national estimates that have risen sharply, surpassing previous reports.^1-4 A primary factor fueling AMR is the misuse of antimicrobials, and antimicrobial stewardship programs (ASPs) are essential for implementing effective and sustained practices for antimicrobial use optimization.^1,5

In general, ASPs have been described in a consensus statement from 3 prominent organizations as interventions created to enhance and measure antimicrobial appropriateness by optimized antimicrobial therapy.⁵ Although adult ASPs have been implemented universally and successfully for decades, formal pediatric-specific ASPs historically have lagged behind these adult programs.^5-8 While improving patient outcomes is important in any patient population, key components of daily ASP program activities have similarities and differences between adults and children.^5,6 This report reviews the prevalence and characteristics of pediatric ASPs throughout the United States, discusses various differences and challenges faced within pediatric ASPs, and describes highlighted strategies and their outcomes for managing ASP efforts in the pediatric population.

Antibiotic Use in Children And Pediatric ASPs

The first human whose life was saved from an infection with an antibiotic was reportedly a 10-month-old infant with Staphylococcus aureus bacteremia that was treated with prontosil rubrum, a compound that is metabolized in vivo to sulfanilamide.^9,10 Since then, the use of antimicrobials in pediatric medicine has increased substantially.¹¹ However, it is important to note the degree and variability in antibiotic use that has been reported.¹² Gerber and colleagues conducted a retrospective cohort study of more than 500,000 pediatric inpatient discharges from 40 freestanding children’s hospitals and found that 60% of all children received 1 or more antibiotics during their admission. Furthermore, antibiotic use varied substantially across the hospitals (38%-72%) following adjustment for both institution- and patient-level demographic/clinical characteristics.¹² Another study conducted by Tribble and colleagues in nearly 35,000 patients across 32 children’s hospitals noted that approximately 25% of the 11,784 hospitalized children who were given an antibiotic received at least 1 suboptimal antibiotic, with the most common inappropriate regimens being overly broad-spectrum empiric therapy, bug–drug mismatch, unnecessary treatment, and/or prolonged surgical prophylaxis.¹³

Historically, this may be partly due to a lack of adequate resources. Newland and colleagues conducted a national, multicenter survey of freestanding children’s hospitals to determine the prevalence of pediatric ASPs throughout the United States.⁷ Following a 91% response rate, formal pediatric ASPs were identified in only 38% of responding institutions with a median number of full-time equivalents being 0.6. However, it is important to note that this study was published approximately 10 years ago, and 36% of the responding children’s hospitals were in the process of implementing a pediatric ASP.⁷ A more recent study reported that 94% of surveyed children’s hospitals had an established pediatric ASP but only 79% of these hospitals included all 7 of the CDC’s core elements (Figure 1), and substantial variability was identified in the allocation of financial support.^8,14

Differences and Challenges

Although both adult and pediatric ASPs have similar objectives, there are notable differences and challenges between the 2 populations (Figure 2), and special considerations specific to infants and children must be recognized when contributing to pediatric stewardship efforts.^5,6,11 First and foremost, there is a preconceived “fear factor” involved for many clinicians who care for children, particularly if they lack adequate training in this patient population. Furthermore, although both adults and children can present with similar infections, the most common infectious etiologies can differ based on age groups and underlying conditions. Next, treatment recommendations can vary (eg, first-line therapy, durations of therapy), and there are drug- and developmental pharmacokinetic-specific considerations with dosing recommendations typically being based on age and weight.^6,11

Although the prevalence of antibiotic resistance is lower than in adults, multiple studies have shown that the national trends of drug-resistant organisms in children are increasing year after year.^15-17 Furthermore, neonates pose even further challenges: “fear factor” to the extreme, nonspecific signs and symptoms of infection, the use of nonspecific biomarkers, culture-negative sepsis, and the possibility of neonatal ICUs within adult hospitals with limited resources and expertise for this patient population.¹⁸ Importantly, there is also a substantial lag in newly published evidence when comparing the infectious diseases literature about the adult population and children.^6,11

There are common ASP and therapeutic strategies performed in adult patients that may not be possible in certain pediatric subgroups. First, certain antibiotics (eg, ceftriaxone, sulfamethoxazole-trimethoprim, fluoroquinolones, tetracyclines) may be restricted in the pediatric population by particular precautions or lack of clinician comfort with use in specific age groups.¹⁷ Although most literature suggests that shorter durations of antimicrobial therapy are noninferior to longer durations of therapy in adults, data comparing shorter and longer durations in the pediatric literature are scant.¹⁰ Additionally, a key component of most ASPs is antimicrobial IV-to-oral conversion, as parenteral administration can be associated with increases in healthcare expenditures, longer hospital length of stay, and an increase in side effects (eg, infection, phlebitis). Furthermore, enteral administration of antimicrobials reduces nursing needs, promotes increased patient satisfaction, and has been deemed safe and effective in most types of infections.¹⁹ However, antimicrobials cannot work if they are not taken, and the tolerance and adherence of children to swallow oral suspensions and/or solid capsules/tablets can be influenced by variables such as age, background, behavior, disabilities, physician concerns, and/or palatability concerns.^20,21

Ensuring the appropriate use of antimicrobials is a key aspect of all ASPs.^5-6,14 In another example, the Infectious Diseases Society of America Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria defines it as “the presence of one or more bacteria growing in the urine at specified quantitative counts (=10⁵ colony-forming units/mL), irrespective of the presence of pyuria, in the absence of signs or symptoms attributable to urinary tract infection.”²² Identifying individuals with asymptomatic bacteriuria and ensuring that they are not prescribed unnecessary antibiotics is a common component of most adult ASPs; however, detection of asymptomatic bacteriuria in the pediatric population poses unique problems. Consequently, many younger, nonverbal patients may be treated for “urinary tract infections” inappropriately due to the inability to verbalize if they are truly symptomatic.^6,22

The Evidence Within Pediatric Antimicrobial Stewardship

The CDC’s Seven Core Elements of Hospital ASP Programs consists of components that are associated with successful ASPs and help institutions achieve the primary goal of most ASPs, which is antimicrobial use optimization.¹⁴ As unnecessary antibiotic use can contribute to the development of antimicrobial resistance and avoidable adverse effects, implementation of an ASP program is an important first step; however, program success should be determined through further evaluation of intervention and acceptance rates, antimicrobial prescribing rates, and clinical outcomes.^6,14

Prospective audit and feedback frequently are incorporated in daily ASP activities and has demonstrated high success rates in numerous adult studies.^5,6 Newland and colleagues conducted a retrospective, quasi-experimental study to evaluate the effect of prospective audit and feedback on antimicrobial use in children.²³ Of nearly 9,000 patients who were reviewed, 2,378 ASP recommendations were made for 1,703 patients with a compliance rate of 92% with agreed-upon ASP recommendations. Specifically, the most common ASP recommendation was to discontinue antibiotics (41%), leading to a 17% reduction in monthly days of therapy per 1,000 patient-days for selected antibiotics.²³

High-priority targets can enable ASPs to provide high impact and timely interventions.^5-16 Particularly, upper respiratory tract infections (URTIs) are a common indication with inappropriate antimicrobial prescribing.²⁴ Ilges and colleagues conducted a quasi-experimental, retrospective study of all outpatient encounters associated with tier 3 (“never prescribe”) URTI diagnoses.²⁵ The intervention included a multifaceted outpatient ASP bundle, which also had syndrome-based, prepopulated order panels. There were more than 165,000 tier 3 encounters reviewed (pre-implementation, 58.0%; post-implementation, 42.0%). Importantly, approximately 50% of all encounters were in children younger than 18 years. Overall, there was a lower rate of antibiotic prescribing that was observed after implementation of the ASP bundle (22% vs 11%).²⁵

“Handshake stewardship” is becoming an increasingly popular strategy to optimize ASP efforts. The general premise is a lack of antimicrobial restriction and/or preauthorization, physician and pharmacist review of all antimicrobials, and then an in-person, rounding-based approach involving feedback with the primary team.²⁶ Importantly, this is a resource-intensive strategy that may be impractical in large adult hospitals but may be more feasible in smaller, children’s hospitals.²⁶ Hurst and colleagues evaluated implementation of a handshake stewardship initiative pre- and post-implementation and found an overall 11% reduction in antimicrobial use, with larger reductions seen with selected antibiotics, including vancomycin (26% reduction) and meropenem (22% reduction).²⁶

Conclusions

A key component of ASPs is to optimize antimicrobial use, improve patient outcomes, and slow the development of antimicrobial resistance, and pediatric ASPs play a crucial role in accomplishing these goals in children.^5,6 Despite historical challenges in the widespread implementation of pediatric ASPs, recent data indicate a significant increase in pediatric-specific ASPs throughout the United States.^7,8 The unique challenges and differences of pediatric care underscore the necessity for tailored strategies that balance ASP efforts with the nuances of pediatric medicine.^5-6,11,18 Pediatric-specific resources, such as the Pediatric Infectious Diseases Society Pediatric ASP Toolkit, provide invaluable support for clinicians aiming to implement or improve their programs, which helps ensure the effective management of antimicrobial use in the pediatric population.²⁷

---

Dr. Morrisette receives grant funding through AbbVie and Stellus Rx, has participated in scientific advisory boards for AbbVie and Basilea Pharmaceutica, and has provided expert witness testimony to Copeland, Stair Valz & Lovell. Dr. Morrisette receives grant funding through AbbVie and Stellus Rx, has participated in scientific advisory boards for AbbVie and Basilea Pharmaceutica, and has provided expert witness testimony to Copeland, Stair Valz & Lovell.

References

1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-655.
2. WHO. Antimicrobial Resistance. Accessed April 7, 2025. https://bit.ly/4dyhpsT
3. CDC. Antibiotic Resistance Threats in the United States, 2019. U.S. Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html
4. CDC. Antibiotic Resistance Threats in the United States, 2013. U.S. Department of Health and Human Services, CDC; 2013. https://bit.ly/3G2CDUc-IDSE
5. Fishman N. Infect Control Hosp Epidemiol. 2012;33(4):322-327.
6. Gerber JS, Jackson MA, Tamma PD, et al. Pediatrics. 2021;147(1):e2020040295.
7. Newland JG, Gerber JS, Weissman SJ, et al. Infect Control Hosp Epidemiol. 2014;35(3):265-271.
8. McPherson C, Lee BR, Terrill C, et al. Antibiotics (Basel). 2018;7(1):4.
9. Northey EH. The Sulfonamides and Allied Compounds. Reinhold Publishing, Inc.; 1948.
10. Davar K, Clark D, Centor RM, et al. Open Forum Infect Dis. 2022;10(1):ofac706.
11. Probst V, Islamovic F, Mirza A. Pediatr Investig. 2021;5(3):229-238.
12. Gerber JS, Newland JG, Coffin SE, et al. Pediatrics. 2010;126(6):1067-1073.
13. Tribble AC, Lee BR, Flett KB, et al. Clin Infect Dis. 2020;71(8):e226-e234.
14. CDC. Core Elements of Hospital Antibiotic Stewardship Programs. US Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/antibiotic-use/healthcare/pdfs/hospital-core-elements-H.pdf
15. Logan LK, Renschler JP, Gandra S, et al. Emerg Infect Dis. 2015;21(11):2014-2021.
16. Logan LK, Gandra S, Mandal S, et al. J Pediatr Infect Dis Soc. 2017;6(4):352-359.
17. Romandini A, Pani A, Schenardi PA, et al. Antibiotics (Basel). 2021;10(4):393.
18. Nash C, Simmons E, Bhagat P, et al. Neoreviews. 2014;15(4):e116-e122.
19. McCarthy K, Avent M. Aust Prescr. 2020;43(2):45-48.
20. Pelco LE, Kissel RC, Parrish JM, et al. J Dev Behav Pediatr. 1987;8(2):90-96.
21. Zajicek A, Fossler MJ, Barrett JS, et al. AAPS J. 2013;15(4):1072-1081.
22. Nicolle LE, Gupta K, Bradley SF, et al. Clin Infect Dis. 2019;68(10):e83-e110.
23. Newland JG, Stach LM, De Lurgio SA, et al. J Pediatric Infect Dis Soc. 2012;1(3):179-186.
24. Felming-Dutra KE, Hersh AL, Shapiro DJ, et al. JAMA. 2016;315(17):1864-1873.
25. Ilges D, Jensen K, Draper E, et al. Open Forum Infect Dis. 2023;10(12):ofad585.
26. Hurst AL, Child J, Pearce K, et al. Pediatr Infect Dis J. 2016;35(10):1104-1110.
27. Pediatric Infectious Diseases Society. Pediatric ASP Toolkit. Accessed April 9, 2025. https://pids.org/pediatric-asp-toolkit/

Copyright © 2025 McMahon Publishing, 545 West 45th Street, New York, NY 10036. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form.